This is a resubmission of an R01 application designed to evaluate the novel radiopharmaceutical, 123I IMPY (IMPY), that binds to the amyloid plaque in patients with Alzheimer's disease (AD). This tracer is the first of its kind for use with single photon emission computed tomography (SPECT) and may have wide applications for the diagnosis and follow up of AD patients. Our preliminary studies demonstrated that IMPY was safe to use in human subjects and had a good biodistribution profile. We also obtained initial SPECT data on 4 AD patients and 3 controls which showed a clear difference between the groups. However, a larger scale trial is necessary in order to better establish the diagnostic accuracy of IMPY. Since the clinical diagnosis of AD is often difficult to make, it is necessary to compare IMPY SPECT results to those of other measures for detecting AD including 18F fluorodeoxyglucose (FDG) positron emission tomography (PET), and other biochemical biomarkers. We plan to perform IMPY SPECT scans on 60 AD patients and 60 control subjects over a four year period. These scans will be analyzed on a number of levels including input function, kinetics, tracer uptake, and best methods to simplify quantitation. The best method for quantifying IMPY uptake and distinguishing AD patients from controls using IMPY SPECT will be determined. This data will help establish the range of uptake of IMPY in AD patients and controls in order to differentiate the two groups. Using receiver operator characteristic curves, we will determine the best method for optimizing diagnostic accuracy. Tracers that target the A2 plaques have been a recent focus of research in the diagnosis of AD and IMPY represents the first 123I labeled compound. Given the wide availability of SPECT imaging, IMPY may have substantial applications for the diagnosis and follow up of AD patients, especially when such patients are treated with medications designed to attenuate the pathophysiological course of the disease. Radioactive tracers that target the A2 plaques for diagnosing Alzheimer's disease (AD) have been a recent primary focus of research. These tracers can aid in the early detection of AD and potentially monitor changes associated with therapeutic interventions. Given the wide availability of SPECT imaging, 123I IMPY may have substantial applications for the diagnosis and follow up of AD patients, and thus, the need to determine its capabilities and the best method for evaluating images is crucial for the future use of this potentially important amyloid imaging tracer.